Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

An improved mixture of gaussian model fo r real time vehicle detection

This paper proposes a novel method to segment video sequences which undergoes gradual changes into foreground and background layers. The background layer contains all objects which have been stationary since the beginning of the video sequence. The foreground layer contains objects which have entered into or move within the video scene and these objects can be moving or stationary. An improved and adaptive Mixture of Gaussian (MoG) model with a feedback mechanism algorithm has been formulated. The MoG model will classify every pixel in the image as belonging either the foreground or the background layer. Every object in the foreground layer will be tracked and updated in the MoG via the feedback mechanism. This feedback avoids stationary foreground objects being updated into the MoG and thus affecting the approximation done by the MoG. This algorithm has been implemented into an Intelligent Transportation System (ITS) to detect vehicles on the road in an outdoor environment. A promising result is obtained in extracting vehicles on the road

ITpreneurship : a new perspective on characteristics of entrepreneurs in IT industry

The current emphasis on entrepreneurship in Singapore has spurred the team into the study of this topic. The team has selected the IT industry because this newly-emerged industry commands high market potential and growth. A second motivation for the study is that Singapore is in need of entrepreneurs who can constantly innovate, experiment, fail, pick themselves up and start all-over again in this industry, which the team denotes as ITpreneurs. Such technically-equipped ITpreneurs who possess the ability to exploit opportunities and confidence to take up major challenges can play an essential role in contributing to the economic development of Singapore.ACCOUNTANC

Nanocrystalline K-F zeolite from rice husk silica as an eco-friendly solid base catalyst for the synthesis of jasminaldehyde under microwave irradiation

Nanocrystalline aluminosilicate F-type zeolite (K-F, EDI-type structure) was synthesized in an organic template-free system using rice husk ash (RHA) silica source and microwave energy. The morphology, crystallite size, chemical composition, crystallographic and basicity properties of the nanocrystals were studied by using various characterization techniques. The results showed that fully crystalline K-F zeolite (Si/Al ratio = 1.26) with flattened cuboid-like shaped could be obtained within 2 min of crystallization which was considerably very fast. In addition, K-F zeolite nanocrystals was also tested as a solid base catalyst in the microwave-enhanced Aldol condensation reaction of heptanal with benzaldehyde and the six catalytic parameters were studied and optimized. The nanosized K-F zeolite crystals showed good catalytic performance in the studied reaction with 77.1% heptanal conversion and 69.5% jasminaldehyde selectivity under optimum reaction condition. The nanocatalyst was reusable and no significant loss in its catalytic reactivity was observed even after five consecutive reaction cycles

Molecular Evolution of Glutathione S-Transferases in the Genus Drosophila

As classical phase II detoxification enzymes, glutathione S-transferases (GSTs) have been implicated in insecticide resistance and may have evolved in response to toxins in the niche-defining feeding substrates of Drosophila species. We have annotated the GST genes of the 12 Drosophila species with recently sequenced genomes and analyzed their molecular evolution. Gene copy number variation is attributable mainly to unequal crossing-over events in the large δ and ɛ clusters. Within these gene clusters there are also GST genes with slowly diverging orthologs. This implies that they have their own unique functions or have spatial/temporal expression patterns that impose significant selective constraints. Searches for positively selected sites within the GSTs identified G171K in GSTD1, a protein that has previously been shown to be capable of metabolizing the insecticide DDT. We find that the same radical substitution (G171K) in the substrate-binding domain has occurred at least three times in the Drosophila radiation. Homology-modeling places site 171 distant from the active site but adjacent to an alternative DDT-binding site. We propose that the parallel evolution observed at this site is an adaptive response to an environmental toxin and that sequencing of historical alleles suggests that this toxin was not a synthetic insecticide

Tropisetron modulation of the glycine receptor: femtomolar potentiation and a molecular determinant of inhibition

The 5-hydroxytryptamine type-3 receptor antagonist tropisetron is in clinical use as an anti-emetic drug. This compound also exerts both potentiating and inhibitory effects on the glycine receptor chloride channel. The inhibitory effects occur at micromolar concentrations, whereas the potentiating effects are shown here to occur at femtomolar concentrations at the homomeric alpha 1 receptor. Potentiation occurred only when tropisetron was applied in the presence of glycine. We also sought to identify molecular determinants of tropisetron inhibition at the alpha 1 glycine receptor by serially mutating residues located in or near known ligand-binding sites. We discovered that conservative mutations to N102 ablated tropisetron inhibition without affecting the magnitude or sensitivity of tropisetron potentiation. Several lines of evidence, including a structure-activity analysis of tropisetron, atropine and SB203186, suggest that N102 may bind to the tropisetron tropane nitrogen via H-bonding. Mutation of the N125 residue in the beta subunit, which corresponds to N102 in the alpha 1 subunit, had little effect on tropisetron inhibitory potency. These results show that N102 is required for tropisetron inhibition but not potentiation and that inhibitory tropisetron binds in different orientations at different subunit interfaces. To our knowledge, tropisetron is the most exquisitely sensitive modulator yet identified for a cys-loop receptor

Effect of Extra-Framework Cations of LTL Nanozeolites to Inhibit Oil Oxidation

Accessed by 12/2015International audienc